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Minimally Invasive Surgical Repair of Vertebral Artery Ostium Stenosis in Patients with
Ischemic Stroke: A Single-Center Case Series
Riste Zimoski
1
, Petar Ugurov
1
, Lidija Veljanoska-Kiridjievska
1
, Nikola Hristov
1
, Enver Idoski
1
, Marko Gjorgon
1
,
Neda Milevska-Kostova
2
, Rodney Alexander Rosalia
1,3
, Zan Mitrev
1
-BACKGROUND: Ischemic stroke is the second leading
cause of death in North Macedonia. Posterior circulation
disease, caused by vertebral artery (VA) ostium (VAo) steno-
sis, is a common cause of ischemic stroke. We established a
treatment approach using surgical revascularization of pos-
terior circulation disease. In the present observational study,
we assessed the outcome after surgical revascularization of
the posterior circulation ischemia caused by VAo stenosis.
-METHODS: A retrospective analysis of 20 consecutive
patients who had undergone surgery from January 2017 to
December 2019. The VA was accessed through a 3-cm
incision in the upper medial clavicle. The corrective pro-
cedures consisted of resection and anastomosis (15 of 20),
VA to subclavian artery transposition (16 of 20), endarter-
ectomy (10 of 20), vein graft interposition techniques (4 of
20), and vein graft bypass (1 of 20).
-RESULTS: The cohort included 9 acute cases. The mean
patient age was 66.5 years (range 46e77). Of the 20 pa-
tients, 8 were women and 12 were men. Left-sided VA
pathology was present in 75% of the cases. We observed
rapid clinical improvement in 19 patients (95%). The total
study period was 321 patient-months, with a median
follow-up of 18 months (interquartile range, 5e24 months).
One patient had died of an unknown cause after 12 months.
During the follow-up period, 15 patients (75%) had reported
permanent clinical improvement with no significant
relapse of symptoms.
-CONCLUSIONS: Minimally invasive surgical revascu-
larization of the posterior brain circulation is a clinically
effective therapeutic approach to manage ischemia caused
by VAo stenosis. It can be performed safely, promote long-
lasting symptom relief, and prevent recurrent strokes.
INTRODUCTION
The global burden of disease study conducted in 2017 re-
ported alarming data for North Macedonia.
1
More people in
North Macedonia die of strokes than of any other cause,
with ischemic stroke representing the second leading cause of
death and disability.
2,3
Nevertheless, neither government policies
nor national guidelines have been established regarding provision
of a stroke service.
4
In the absence of a national stroke program,
we have established a prevention and treatment approach based
on surgical revascularization that targets the posterior circulation
ischemia in particular.
5
The posterior circulation is supplied by the vertebral arteries
(VAs). Posterior circulation disease (PCD) will be observed in
Key words
-Extracranial
-Minimally invasive surgery
-Posterior circulation disease
-Vertebral artery
Abbreviations and Acronyms
CT: Computed tomography
CTA: Computed tomography angiography
CVI: Cerebrovascular insult
IQR: Interquartile range
PCD: Posterior circulation disease
SV: Saphenous vein
TIA: Transient ischemic attack
VA: Vertebral Artery
VAo: Vertebral artery ostium
From the
1
Department of Cardiovascular Surgery, Zan Mitrev Clinic; and
2
Institute for Social
Innovation, Skopje, Republic of North Macedonia; and
3
Maastricht School of Management,
Maastricht, The Netherlands
To whom correspondence should be addressed: Zan Mitrev, M.D.
[E-mail: zan@zmc.mk]
Supplementary digital content available online.
Riste Zimoski, Petar Ugurov, Rodney Rosalia, and Zan Mitrev contributed equally to the
present study.
Citation: World Neurosurg. (2020).
https://doi.org/10.1016/j.wneu.2020.11.041
Journal homepage: www.journals.elsevier.com/world-neurosurgery
Available online: www.sciencedirect.com
1878-8750/ª2020 The Authors. Published by Elsevier Inc. This is an open access article under
the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
WORLD NEUROSURGERY -:---,-2020 www.journals.elsevier.com/world-neurosurgery 1
Doing More with Less
20%e40% of cases of stroke.
6
The flow characteristics and
morphology of the subclavian artery and VA predispose to the
formation of atherosclerotic lesions at the VA ostium (VAo).
Thus, the VAo and the proximal segment (V1) are the most
common sites of stenosis observed in patients after
ischemic stroke resulting from posterior circulation
insufficiency.
6-10
Posterior circulation stroke causes
awiderangeofnonspecific presenting symptoms;
thus,misdiagnosisiscommon.
11
PCD caused by VAo stenosis often manifests as a
medically refractory condition requiring intervention.
The optimal treatment of VAo stenosis is ill-defined.
However, long-term clinical benefit likely requires complete
removal of ostial plaques, which will often extend deep into the
subclavian artery.
12
Despite the clinical benefits associated with endovascular
treatment approaches for PCD, stenting for VAo stenosis is
infrequently performed in North Macedonia because of limited
nationwide expertise with VA stenting. In our attempt to
compensate for the limited experience with VA endovascular
interventions and to provide a durable, clinically effective
treatment alternative, we have established an open surgical
repair technique to treat VAo stenosis and posterior circulation
ischemia. Surgery has the potential to offer sustained, relapse-
free postoperative clinical outcomes comparable to those with
endovascular procedures.
13,14
However, the approach is rarely
performed owing to the complexity, perceived risks, and high
rate of complications.
15
In the present report, we have
described our experience with surgical correction of the
proximal VA in the management of ischemic strokes
attributable to PCD.
METHODS
Study Cohort
The study case series included 20 consecutive patients who had
undergone surgery on the VA under general anesthesia from 2017
to 2019. Data were collected prospectively using the electronic
health records and analyzed retrospectively. The primary
endpoint was a debilitating stroke in the first 30 days after
discharge. The secondary endpoints were operative mortality,
16
mid-term all-cause mortality, ischemic stroke during the
follow-up period, target vessel revascularization, and symptom
relapse.
The decision to perform surgery was determined by the pres-
ence of persistent neurological symptoms (>3 months), despite
adequate first-line medical therapy, combined with a history of
ischemic events, confirmed ischemic zones on computed to-
mography (CT) of the brain, >50% stenosis in both VAs, and/or
>60% unilateral stenosis in the dominant VA.
17
Asymptomatic
patients with severe or critical disease with 70% VAo stenosis
in the dominant artery discovered incidentally were informed of
their high risk of stroke and advised to undergo invasive
treatment.
The ethical committee of the hospital approved the present
observational study.
18
Diagnostic Approach
All patients were diagnosed according to their clinical
symptoms and CT angiography (CTA) findings of the
vertebrobasilar area.
Surgical Technique
We used a minimally invasive approach for the surgery
(Video 1). In brief, the patients were sedated and
placed under general anesthesia. We intubated the
patients 30e60 minutes before surgery and extubated them
during the 30e120 minutes of postoperative recovery in the
intensive care unit.
Intraoperative monitoring was performed via 5-lead electrocardi-
ography, noninvasive blood pressure, pulse oximetry, and peripheral
insertion of an 18-gauge intravenous cannula. In addition, a 20-gauge
cannula was placed in the contralateral radial artery for continuous
invasive blood pressure monitoring. We monitored the cerebral
oxygenation and circulation using near-infrared spectroscopy.
The patient’s head was placed in a supine position with slight
hyperextension and contralateral rotation. The VA lesion site was
accessed via a 3-cm inclined incision in the upper medial clavicle,
followed by cutting the platysma. Special care was taken not to
injure the thoracic duct when performing surgery on the left VA.
The lateral head of the sternocleidomastoid muscle was dissected,
followed by visualizing the phrenic nerve, which was isolated
medially to liberate space to cut the anterior scalene muscle.
Resection of the anterior scalene muscle allowed for access and
evaluation of the subclavian artery, which is mobilized medially.
Several lateral branches were ligated next to enable visualization of
the origin of the VA. Approximately 10 minutes before clamping of
any of the major vessels, we administered 4000e10,000 IU of
heparin to establish an activated clotting time of >300 seconds.
The VA was anatomically characterized by the lack of branches
in the proximal segment. Once identified, the VA was isolated,
liberated from any adhesions, and mobilized. The subclavian ar-
tery was clamped proximally and distally with vascular clamps,
and the VA was clamped with a bulldog clamp. The VA was
transected at its origin, and several corrective procedures were
performed as indicated by the lesion characteristics.
19-24
Endarterectomy. Endarterectomy and reimplantation of the prox-
imal VA are established vascular procedures (Figure 1). We
routinely inspected the lumen of the subclavian artery for
abnormalities. The vessel was irrigated with heparinized saline.
Decalcification and endarterectomy were performed, if necessary.
Transposition. The VA artery was transposed to the subclavian
artery via a terminalelateral anastomosis (Figure 1). We used 8-0
Prolene suture for the anastomosis. Before full closure of the
suture line, the distal subclavian artery was unclamped and de-
aired by back-bleeding.
Video available at
www.sciencedirect.com
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DOING MORE WITH LESS
RISTE ZIMOSKI ET AL. SURGICAL REPAIR OF VERTEBRAL ARTERY OSTIUM STENOSIS
Bypass. The saphenous vein (SV) was used as the conduit for the
subclavian artery to VA bypass, which was performed using
interposition techniques as previously described. In brief, the SV
was exposed at the medial aspect of the knee and thigh. The vein
was ligated next, and its lumen was flushed and distended with
heparinized saline solution. We harvested ~5e10 cm in length.
On exposure of the VA, we prepared the subclavian artery as an
inflow for a bypass graft. The VA was clampedith 2 clips, and next
VA was incised, followed by continuous anastomosis with the SV
graft in a side-to-end fashion, using 8-0 Prolene sutures. Next, we
clamped the subclavian artery at a proximal and distal site around
the area planned for the arteriotomy. The cut was made using a
no. 11 blade and completed with a 4-mm diameter arteriotomy
punch. Subsequently, an end-to-side anastomosis was performed
with the SV graft using continuous 7-0 Prolene sutures to the
subclavian artery in the same manner.
Interposition. The exposure, identification, and isolation of the
subclavian artery and VA were performed as described previously.
The occluded section of the VA was identified. Using the harvested
SV, we performed a side-to-end anastomosis on a proximal part of
the subclavian artery using a 7-0 running Prolene suture. The
distal part of the graft was connected to the VA via an end-to-end
anastomosis using 8-0 Prolene suture.
The arterial clamps were released, a drainage tube was placed in
the surgical site, and the wound was closed. Finally, heparin-
ization was nullified by the administration of 2500e5000 IU of
protamine to achieve an activated clotting time of <160 seconds.
Statistical Analysis
We used Prism, version 8.3.1 (GraphPad, San Diego, California,
USA), for statistical analysis. The D’Agostino and Pearson
normality test was used to assess continuous data distribution.
Categorical data are presented as the number of events per the
total number with percentages. Continuous data are presented as
the mean standard deviation or median and interquartile range
(IQR). The Fisher exact test was used to compare categorical
variables. We determined survival and freedom-from-reoperation
using the Kaplan-Meier method. Patients were censored at the
last confirmed date of patientephysician contact or telephone
follow-up.
RESULTS
Demographics and Clinical Characteristics
The patient demographics and clinical characteristics are pre-
sented in Table 1. The mean age of the cohort was 66.5 years. Most
of the patients were overweight; 7 had presented with a body mass
index >30 kg/m
2
. Other prominent comorbidities were
hypertension (100%), hyperlipidemia (90%), and type 2 diabetes
mellitus (30%). Three patients had presented with peripheral
artery disease and five (25.0%) with confirmed coronary artery
disease. Two patients had a history of myocardial infarction.
The predominant symptoms at admission were vertigo (80%),
ataxia (25%), and syncope (20%). One asymptomatic patient with a
history of transient ischemic attack (TIA) was treated after obser-
vation of hypodense zones on the patient’s CT scans of the brain
during assessment for elective cardiac surgery. He was considered
at high risk for recurrent cerebrovascular insult (CVI)/TIA because
of the presence of soft plaque atherosclerosis at the VAo.
The active medical treatments at admission are described in
Table 2. Despite ongoing medical therapy, the patients reported
not experiencing a decrease in symptom severity. The CTA
examinations (Figure 2) revealed unilateral left- and right-sided
lesions in 9 patients (45.0%) and 5 patients (25.0%), respec-
tively, with bilateral VAo/V1 lesions in 5 patients. For the patients
with bilateral lesions, we first targeted the dominant VA.
The corrective surgical approaches are presented in Table 3.We
mainly performed complete resection of the stenotic lesions
combined with VA to subclavian artery transposition and
terminalelateral anastomosis. Other procedures included endar-
terectomy, graft interposition techniques, and 1 case of vein
bypass grafting.
Early Clinical Outcomes
The surgery duration was, on average, 70.2 16.8 minutes. The
patients had required 3.29 hours (IQR, 2.85e3.79 hours) of me-
chanical respiratory support. The postoperative intensive care unit
length of stay was 4.7 hours (IQR, 3.9e16.5 hours), and the
average hospital stay was 2 days (IQR, 2e3 days).
Surgery resulted in direct clinical success for 19 of 20 patients
(95.0%), leading to immediate symptom relief. CTA follow-up
analysis was available for 14 patients (70.0%). In this subgroup,
adequate VA patency was confirmed. The case of a patient with an
occluded right VA treated at our clinic is shown in Figure 2BeE.
Adequate graft patency was confirmed after surgical
revascularization. The 30-day follow-up data were complete for
all but 1 patient. The latter patient had not presented for her
postoperative follow-up visit. She had relocated after the surgery
and changed her telephone number and contact details without
informing us.
No patient had died early in the follow-up period. One woman
who had previously undergone coronary artery bypass grafting and
left carotid artery endarterectomy had experienced persisting
symptoms due to de novo atherosclerotic lesions in the carotid
arteries. Medical therapy was insufficient to mitigate the symp-
toms, and she successfully underwent a second surgery on the left
common and internal carotid arteries after 9 months. We inter-
viewed her 18 months after the index VA surgery. Her clinical
condition was suboptimal with high blood pressure, and she was
experiencing bouts of dizziness. One male patient had required
second surgery on the contralateral VA. We performed
Figure 1. Intraoperative images showing open surgical repair on the dominant right stenotic vertebral artery ostium of a 69-year-old man who had
presented with recent transient ischemic attack and a history of stroke attributed to bilateral vertebral artery ostium stenoses. (A) Assessing and
determining the position of the cut; (B) cutting the skin and subcutaneous tissue; (CeG) preparation of the tissue and visualiza tion and mobilization
of the subclavian artery; (H, I) visualization and mobilization of the vertebral artery; (J) placement of the clamps; (KeO) resection of the vertebral
artery, endarterectomy, and anastomosis; (P, Q) hemostasis control; (R, S) placement of the drainage tube; and (T, U) closure of the wound.
4www.SCIENCEDIRECT.com WORLD NEUROSURGERY,https://doi.org/10.1016/j.wneu.2020.11.041
DOING MORE WITH LESS
RISTE ZIMOSKI ET AL. SURGICAL REPAIR OF VERTEBRAL ARTERY OSTIUM STENOSIS
endarterectomy and longitudinal, transverse resection of the right
subclavian artery and VA arterioplasty with the subclavian artery
(Figure 2FeI).
Mid-Term Follow-Up
The total follow-up period was 321 patient-months, with a median
follow-up of 18 months (IQR, 5e24 months; Figure 3A). No
confirmed cases of stroke or other debilitating neurological
events related to the index VAo/V1 surgery had occurred. Of the
20 patients, 16 (80.0%) reported durable symptom resolution
with no significant relapse of neurological symptoms. Of the 4
patients with symptom relapse, 2 had successfully undergone
surgery of carotid artery stenosis, which had manifesting as
new-onset vertigo. One of the 2 patients, a man who had under-
gone reoperation 4 months after the index surgery, had died of an
unknown cause 8 months after the second surgery. However, his
relatives were unwilling to disclose the cause of death.
During the whole study period, 6 patients were readmitted for
other cardiovascular interventions or surgery (Figure 2B). One
patient with coronary artery disease who had undergone
coronary artery bypass grafting 5 years before the index VA
surgery was then admitted twice within 3 months because of
paroxysmal supraventricular tachycardia and on a subsequent
occasion because of paroxysmal atrial fibrillation. These events
were managed successfully with antiarrhythmic therapy.
DISCUSSION
In North Macedonia, more people die of stroke than of any other
cause
3
(Supplementary Figure 1). A global comparison, using a
comparable social-demographic index, suggested that the stroke
death rates in North Macedonia are substantially higher than those
in other countries (Supplementary Figure 1B). Mortality after
ischemic strokes is observed frequently throughout the Balkan
peninsula (Supplementary Table 1). Ischemic stroke is the second
leading cause of death in North Macedonia.
PCD due to VAo stenosis is the second most common cause of
stroke.
8-10
Lifestyle factors, including smoking, alcohol consump-
tion, unhealthy diet, and sports, play a crucial role in the devel-
opment and progression of atherosclerosis and the risk of stroke.
25
In North Macedonia, a substantial proportion of the population
smokes
26
and, similar to the neighboring countries,
27,28
an active
lifestyle combined with a healthy diet is practiced only by a few
of the population. Consequently, the incidence of cardiovascular
disease and stroke has been increasing.
5,26,29
The physiological mechanisms leading to PCD are strongly
associated with the presence of atherosclerosis. Distal VA
atherosclerotic lesions have been reported; however, plaque de-
positions at the proximal segment have been observed most
often.
30-33
Table 1. Demographics and clinical characteristics (n¼20)
Variable Value
Age (years)
Full cohort 66.5 (46e77)
Male (n¼12) 61 (46e77)
Female (n¼8) 67.5 (52e77)
Weight (kg) 76.5 14.31
Height (m) 1.65 0.1
BMI (kg/m
2
) 28.2 4.86
Symptoms
Acute stroke 9 (45.0)
TIA 2 (10.0)
Vertigo 19 (95.0)
Syncope 4 (20.0)
Ataxia 5 (25.0)
Tinnitus 3 (15.0)
Scotoma 3 (15.0)
Diplopia 1 (5.0)
Comorbidity
Smoking 4 (20.0)
Diabetes mellitus 6 (30.0)
COPD 1 (5.0)
Arterial hypertension 20 (100)
Hyperlipidemia 18 (90.0)
Previous myocardial infarction 2 (10.0)
Peripheral artery disease 3 (15)
Coronary artery disease 5 (25.0)
Previous myocardial infarction 2 (10.0)
LMCA >50% stenosis 0 (0)
LAD >50% stenosis 5 (25.0)
Cx >50% stenosis 3 (15.0)
RCA >50% stenosis 4 (20.0)
LVEF (%) 54.1 7.8
Data presented as mean (range), mean standard deviation, or n(%).
BMI, body mass index; COPD, chronic obstructive pulmonary disease; Cx, circumflex ar-
tery; LAD, left anterior descending artery; LMCA, left main coronary artery; LVEF, left
ventricle ejection fraction; RCA, right coronary artery; TIA, transient ischemic attack.
Table 2. Preoperative Medical Therapy (n¼20)
Medication n(%)
Lipid-lowering therapy 15 (75)
Antiplatelet therapy (aspirin) 9 (45)
SAPT (clopidogrel) 7 (35)
DAPT 1 (5.0)
Antihypertensive therapy 18 (90.0)
DAPT, dual-antiplatelet therapy; SAPT, single-antiplatelet therapy.
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We have described a minimally invasive surgery to resolve
extracranial VA stenosis causing PCD. Our procedure differs from
classic reports of VA surgery. We have opted for a 3-cm incision,
smaller than that originally reported for open surgical repair (5-7
cm).
34
In our experience, we were able to maintain an adequate
surgical view by stabilizing the incision site using the surgical
retractor, which supports recovery and allows for a more
aesthetic scar.
The corrective procedures we used consisted of resection and
anastomosis, endarterectomy, VA artery to subclavian artery
transposition, vein graft interposition techniques and bypass.
Several surgical techniques have been pioneered to treat VAo/V1
segment stenosis. A nonexhaustive list includes VA endarterec-
tomy,
35
VA to subclavian artery transposition,
36
transposition to
the common carotid artery,
10,37
vein bypass grafting from the
subclavian artery, and graft interposition techniques.
38,39
We typically combined multiple procedures, including trans-
position of the VA to the subclavian artery in 16 cases (Table 3).
Others have described VA transposition to the common carotid
artery as a successful technique to revascularize the posterior
circulation.
10,37
However, we have favored direct transposition of
the VA to a distal site on the subclavian artery to preserve the
native anatomy and posterior circulation flow characteristics as
much as possible. Furthermore, the technique we used is the
least invasive because it circumvents the necessity to clamp the
carotid artery. Mirroring our clinical observations, others have
reported that the technique is associated with long-term symp-
tom relief.
22
The indications for surgery account for the symptoms attribut-
able to PCD. Nevertheless, 1 case involved an asymptomatic
71-year-old man with significant plague depositions at the right
VAo, a history of CVI, and >70% stenosis in both internal carotid
arteries. After careful evaluation, with consideration of the high
risk of posterior circulation stroke and the patient’s multiple
comorbidities, we performed graft interposition using the
saphenous vein.
40
Figure 2. (A) Computed tomography of the brain and (B) pre- and (C)
postoperative images of a patient who had undergone surgery twice to
resolve vertebrobasilar disease caused by significant calcification and
plaque deposition that had resulted in near-complete occlusion of the right
vertebral artery (VA). (D,E) Revascularization was achieved via
endarterectomy and longitudinal, transverse resection of the right
subclavian artery, followed by VA arterioplasty with the subclavian artery.
(F,G) The second procedure on the left VA was performed to resolve VA
ostium occlusion that had extended into the subclavian artery. (H,I) Left VA
pathology was treated using an autologous bypass bridge to the subclavian
artery.
Table 3. Surgical Details (n¼20)*
Variable n(%) or Median (IQR)
Operative findings
Stenosis 18 (90.0)
Occlusion 2 (10)
Kinking 2 (10)
Combined surgical corrective procedures
Vertebral artery to subclavian artery transposition 16 (80.0)
Resection and anastomosis 15 (75.0)
Vertebral artery thromboendarterectomy 10 (50.0)
Vein graft interposition techniques 4 (20.0)
Vein graft bypass 1 (5.0)
General anesthesia 20 (100)
Perioperative bleeding (<24 hours; mL) 15 (0e100)
IQR, interquartile range.
*Some patients had multiple vertebral artery ostium/V1 pathologies.
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The treatment options for posterior circulation ischemia caused
by VAo stenosis have increased in the previous decade.
6,33
Stenting
is feasible, despite the technical challenges related to the
morphology of the subclavian and proximal VAs. Nevertheless, 2
randomized trials
8,9
and preplanned pooled individual patient
data analysis evaluating VA stenting
41
failed to show evidence of a
benefit for stroke prevention compared with medical therapy. The
results from recent single-center observational studies have
offered a promising outlook on the use of endovascular procedures
for VAo stenting.
8,9,42
Thus, stenting for extracranial VA stenosis
might be beneficial; however, larger randomized controlled trials
are required to determine treatment success.
41
Collectively, both surgery and endovascular interventions can
lead to durable clinical outcomes, allowing for a personalized
revascularization strategy for PCD. Such a patient-centered
approach would substantially enhance the quality of care for
patients who have experienced stroke in North Macedonia.
However, endovascular proceduresforPCDarenotacommon
practice in North Macedonia. Advanced healthcare is still in
development, and, currently, experience is insufficient to
perform routine stenting of the VAs. The existing strategies used
bytheMinistryofHealthhavefailedtoimprovetheclinical
outcomes after ischemic stroke. A paucity of policies exist
focusedontheprovisionofstroke services or a national stroke
prevention program.
3,5
Our approach offers a treatment option for posterior circulation
ischemic events. The use of open surgical repair offers rapid relief
from neurological symptoms and prevents recurrent TIA/CVI. The
long-term results have been promising, with a total of 321 patient-
months, 15 patients had confirmed durable symptom-free status.
Figure 3. Mid-term survival, freedom from reoperation,
and reason for rehospitalization after vertebral artery
surgery. (A) Long-term survival (blue curve) and
event-free survival (red curve). Follow-up consisted of
321 patient-months (median, 18 months; interquartile
range, 5e24 months). Of 20 treated patients, 6 had
required rehospitalization during the follow-up period
for a cardiovascular pathology. Five had required
surgery. (B) Pie chart showing reasons for
rehospitalization; each readmission and the single
mortality case were scored as an event (red curve).
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STUDY STRENGTHS AND LIMITATIONS
The results of the present study were inevitably associated with the
limitations of single-center observational studies.
43
Although we
have established that the procedure is clinically effective, long-
term CTA examinations of all patients to confirm adequate flow
characteristics would have benefited the study results. Nonethe-
less, the present case series has offered promising results and
guidance on how to manage posterior circulation ischemia in the
absence of well-established endovascular treatment options. Also,
the reported stroke recurrence-free rate and clinical outcomes
have been encouraging and on par with the results obtained from
neurosurgery center of excellence.
7,10,14,44
The observed relapse-
free survival rate was noteworthy; thus, the described technique
might become a valuable approach to curb the “stroke pandemic”
in North Macedonia.
CONCLUSIONS
The minimally invasive surgical repair of VAo/V1 stenosis is a safe
and clinically effective option to treat patients at high risk of
posterior ischemic events in developing countries, such as North
Macedonia. Our treatment approach represents a valuable alter-
native for patients in the absence of a nationwide effective stroke
prevention and treatment program.
CRediT AUTHORSHIP CONTRIBUTION STATEMENT
Riste Zimoski: Data curation, Investigation, Methodology, Valida-
tion, Writing - original draft, Writing - review & editing. Petar
Ugurov: Conceptualization, Investigation, Project administration,
Validation, Visualization, Writing - original draft. Lidija Veljanoska-
Kiridjievska: Investigation, Validation, Visualization. Nikola
Hristov: Supervision. Enver Idoski: Project administration, Super-
vision. Marko Gjorgon: Supervision, Writing - original draft. Neda
Milevska-Kostova: Conceptualization, Investigation, Writing - re-
view & editing. Rodney Alexander Rosalia: Conceptualization, Data
curation, Formal analysis, Investigation, Methodology, Project
administration, Resources, Software, Supervision, Validation,
Visualization, Writing - original draft, Writing - review & editing.
Zan Mitrev: Conceptualization, Investigation, Methodology, Project
administration, Resources, Supervision, Validation, Visualization,
Writing - original draft, Writing - review & editing.
ACKNOWLEDGMENTS
We thank Drs. Atanas Stojanov and Milan Klimkarov for data
collection and screening of medical history files. The single-center
registry containing all data can be shared by the editorial team on
reasonable request.
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Conflict of interest statement: Zan Mitrev is hospital director
at the Zan Mitrev Clinic. The remaining authors declare that
the article content was composed in the absence of any
commercial or financial relationships that could be construed
as a potential conflict of interest.
Presented as a preliminary analysis in poster format and
awarded third place prize at the Bulgarian Society for
Endovascular Therapy and International Association of
Endovascular Specialists Endovascular Academy 2019.
Received 10 June 2020; accepted 7 November 2020
Citation: World Neurosurg. (2020).
https://doi.org/10.1016/j.wneu.2020.11.041
Journal homepage: www.journals.elsevier.com/world-
neurosurgery
Available online: www.sciencedirect.com
1878-8750/ª2020 The Authors. Published by Elsevier Inc.
This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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APPENDIX
Supplementary Table 1. Burden of Ischemic Stroke in Macedonia and the Balkans in 2017
Country
Death (n;%)
OR (95% CI); PValue (Fisher’s Exact Test; NMK vs. Comparator)All-Cause Ischemic Stroke
Macedonia (NMK) 19,111 2412 (12.62) NS
Albania 21,757 739 (3.40) 4.11 (3.78e7.28); <0.0001
Bosnia and Herzegovina 37,011 5365 (14.50) 0.85 (0.81e0.90); <0.0001
Bulgaria 107,619 12,809 (11.90) 1.07 (1.02e1.12); <0.0001
Croatia 51,211 3755 (7.33) 1.82 (1.73e3.19); 0.0051
Greece 120,258 8427 (7.01) 1.92 (1.83e2.01); <0.0001
Montenegro 6502 318 (4.90) 2.81 (2.49e3.17); <0.0001
Serbia 123,685 19,410 (15.69) 0.78 (0.74e0.81); <0.0001
Slovenia 19,904 1120 (5.63) 1.09 (1.07e1.11); <0.0001
CI, confidence interval; NMK, Republic of North Macedonia; NS, not significance; OR, odds ratio.
Data from the Global Burden of Disease Study 2017 Results.
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Supplementary Figure 1. (A) Top 10 causes of death in 2017
and the percentage of change from 2007 to 2017. The data
shown encompasses all ages. (B) Heat map showing top
10 causes of death and disability (disability-adjusted
life-years) for Republic of North Macedonia countrywide
analysis in 2017, which can be used to compare
disability-adjusted life-years across locations relative to the
group average. Comparison groups were chosen according
to the global burden of disease regional classifications,
known trade partnerships, and sociodemographic
indicators: blue, significantly lower than high-middle
sociodemographic index mean; gray, statistically
indistinguishable from sociodemographic index mean; red,
significantly greater than the sociodemographic index
mean (available at: http://www.healthdata.org/
macedonia
3
).
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